rs2305743

Variant names:

• chr19-18082381-G-A
• rs2305743
• NM_005535.3:c.125-117C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-18082381-G-A
• chr19-18082381-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005535.3(IL12RB1):​c.125-117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 707,256 control chromosomes in the GnomAD database, including 13,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2772 hom., cov: 31)
  • Exomes 𝑓: 0.19 (10894 hom.)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37

Genes affected

IL12RB1 (HGNC:5971): (interleukin 12 receptor subunit beta 1) The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-18082381-G-A is Benign according to our data. Variant chr19-18082381-G-A is described in ClinVar as [Benign]. Clinvar id is 2688457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB1	NM_005535.3	c.125-117C>T		intron_variant	Intron 2 of 16	ENST00000593993.7	NP_005526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB1	ENST00000593993.7	c.125-117C>T		intron_variant	Intron 2 of 16	1	NM_005535.3	ENSP00000472165.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28405 AN: 151768 Hom.: 2768 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.193 AC: 107155 AN: 555370 Hom.: 10894 AF XY: 0.190 AC XY: 56927 AN XY: 299526

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.187 AC: 28429 AN: 151886 Hom.: 2772 Cov.: 31 AF XY: 0.186 AC XY: 13815 AN XY: 74228

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.181

Alfa AF: 0.201 Hom.: 6445

Bravo AF: 0.178

Asia WGS AF: 0.130 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.84
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2305743; hg19: chr19-18193191; COSMIC: COSV59097571; COSMIC: COSV59097571;